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Infection and Immunity, November 2004, p. 6538-6545, Vol. 72, No. 11
0019-9567/04/$08.00+0     DOI: 10.1128/IAI.72.11.6538-6545.2004
Copyright © 2004, American Society for Microbiology. All Rights Reserved.

Modeling the Development of Acquired Clinical Immunity to Plasmodium falciparum Malaria

Michelle L. Gatton1,2* and Qin Cheng3

Australian Centre for International & Tropical Health & Nutrition, University of Queensland, Herston,1 Division of Infectious Diseases and Immunology, Queensland Institute of Medical Research, Royal Brisbane Hospital, Brisbane,2 Department of Drug Resistance and Diagnostics, Australian Army Malaria Institute, Gallipoli Barracks, Enoggera, Queensland, Australia3

Received 8 June 2004/ Returned for modification 1 August 2004/ Accepted 4 August 2004

Individuals living in regions where malaria is endemic develop an acquired immunity to malaria which enables them to remain asymptomatic while still carrying parasites. Field studies indicate that cumulative exposure to a variety of diverse Plasmodium parasites is required for the transition from symptomatic to asymptomatic malaria. This study used a simulation model of the within-host dynamics of P. falciparum to investigate the development of acquired clinical immunity under different transmission conditions and levels of parasite diversity. Antibodies developed to P. falciparum erythrocyte membrane protein 1 (PfEMP1), a clonally variant molecule, were assumed to be a key human immunological response to P. falciparum infection, along with responses to clonally conserved but polymorphic antigens. The time to the development of clinical immunity was found to be proportional to parasite diversity and inversely proportional to transmission intensity. The effect of early termination of symptomatic infections by chemotherapy was investigated and found not to inhibit the host's ability to develop acquired immunity. However, the time required to achieve this state was approximately double that compared to when no treatment was administered. This study demonstrates that an immune response primarily targeted against PfEMP1 has the ability to reduce clinical symptoms of infections irrespective of whether treatment is administered, supporting its role in the development of acquired clinical immunity. The results also illustrate a novel use for simulation models of P. falciparum infections, investigation of the influence of intervention strategies on the development of naturally acquired clinical immunity.

* Corresponding author. Mailing address: Malaria and Scabies Group, Queensland Institute of Medical Research, PO Royal Brisbane Hospital, Queensland 4029, Australia. Phone: 61 7 3362 0416. Fax: 61 7 3362 0104. E-mail: michellG{at}qimr.edu.au.

Editor: W. A. Petri, Jr.

Infection and Immunity, November 2004, p. 6538-6545, Vol. 72, No. 11
0019-9567/04/$08.00+0     DOI: 10.1128/IAI.72.11.6538-6545.2004
Copyright © 2004, American Society for Microbiology. All Rights Reserved.



This article has been cited by other articles:

  • GATTON, M. L., PETERS, J. M., GRESTY, K., FOWLER, E. V., CHEN, N., CHENG, Q. (2006). DETECTION SENSITIVITY AND QUANTITATION OF PLASMODIUM FALCIPARUM VAR GENE TRANSCRIPTS BY REAL-TIME RT-PCR IN COMPARISON WITH CONVENTIONAL RT-PCR.. Am J Trop Med Hyg 75: 212-218 [Abstract] [Full Text]  


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